REVIEW Open Access

Medicine in the early twenty-first century:paradigm and anticipation - EPMA positionpaper 2016Olga Golubnitschaja1,2,3*, Babak Baban1,4,5, Giovanni Boniolo1,6,7, Wei Wang1,8,9,10,11, Rostyslav Bubnov1,12,13,Marko Kapalla1, Kurt Krapfenbauer1, Mahmood S. Mozaffari1,4,5 and Vincenzo Costigliola1,14

Keywords: Traditional complementary alternative medicine, Person-centred medicine, Individualised medicine,Stratified medicine, Personalised medicine, Precision medicine, Predictive, preventive, and personalised medicine,Advantage, Limitation, Implementation

BackgroundChallenges of “standardisation” and “individualisation”have always been characteristic for medical services. Interms of individualisation, the best possible individualcare is the ethical imperative of medicine, and it is agood right of any patient to receive it. However, in termsof standardisation, all the available treatments are basedon guideline recommendations derived from large multi-centre trials with many thousands of patients involved.In the most optimal way, the standardisation and indi-vidualisation should go hand-in-hand, in order to iden-tify the right patient treating him/her with the rightmedication and the right dose at the right time point!Further, in paradigm and anticipation, there is a big

discrepancy between “disease care” and “health care”which dramatically impacts ethical and economical as-pects of medical services.Several approaches have been suggested in ancient

and modern medicine to conduct medical services in apossibly optimal way. What is the difference amongstall of them and how big is the potential beyond corre-sponding approach to satisfy the needs of the individ-ual, the patient, professional groups involved andsociety at large?On behalf of the “European Association for Predictive,

Preventive and Personalised Medicine,” the dedicated

EPMA working group provides a deep analysis in the issuefollowed by the expert recommendations considering themultifaceted aspects of both “disease care” and “healthcare” practices including ethics and economy, life qualityof individuals and patients, interests of professional groupsinvolved, benefits of subpopulations, health care system(s)and society as a whole.

Traditional, complementary and alternativemedicine (TCAM)TCAM, also called “integrative medicine,” is consid-ered as an amorphous concept comprising a range ofancient, long-standing but still evolving treatmentapproaches being practised mainly in their countries oforigin as well as in countries into which correspondingexpertise has been “imported” [1]. TCAM refers tohealth practices, approaches, knowledge and beliefsincorporating plant-, animal- and mineral-based medicines,spiritual therapies, manual techniques and exercise(e.g. in form of acupuncture, dietary therapy, herbalmedicine, moxibuston, TaiJi, Ayurveda, amongstothers) applied singularly or in combination to diag-nose, treat and prevent illnesses or maintain well-being [2]. However, the educational level of the doctoris critical for the quality of TCAM that depends onthe national/local curricula varying substantially fromcountry to country and, therefore, may not be ad-equate enough to fully realise potential benefits ofvarious forms of TCAM modalities. TCAM approachesare frequently considered as being non-evidence based[3]. Further deficiencies arise from evident philosophicaland religious differences as well as some cultural barriers

* Correspondence: Olga.Golubnitschaja@ukb-uni-bonn.de1European Association for Predictive, Preventive and PersonalisedMedicine, Brussels, Belgium2Radiologic Department, Rheinische Friedrich-Wilhelms-University of Bonn,Sigmund-Freud-Str. 25, 53105 Bonn, GermanyFull list of author information is available at the end of the article

© The Author(s). 2016 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, andreproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link tothe Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Golubnitschaja et al. The EPMA Journal (2016) 7:23 DOI 10.1186/s13167-016-0072-4

between the countries of origin and countries into whichTCAM is “imported” [1]. Nevertheless, in addition to theconventional medicine, TCAM is getting more and morepopular and well-pursued in Western countries. Fromview point of predictive and preventive medicine, TCAMprovides a unique expertise for recognising the so-calledsuboptimal health conditions before a clinical manifest-ation of severe pathologies [3–5]. These global trendsmake particularly attractive consideration regardinginnovative hybrid approaches which would utilise advan-tages of both TCAM and modern medicine and, therefore,benefiting patients and enriching the spectrum of toolsand overall expertise of the dedicated professional groupsassuring the reproducibility of TCAM technologies andoutcomes [6]. However, those approaches are currentlyunderdeveloped and require additional major efforts interms of multi-professional collaboration, scientific andtechnological discoveries and extensive financial support.

Person-centred medicineThe main idea of the person-centred medicine is topromote health and, therefore, reduce disease burden. Inthis concept, any health condition is considered as anindividual state of physical, mental, social and spiritualwell-being. Contextually, health care approaches areprioritised by person-centred medicine compared to adisease care. Humanistic interpretation of medicine ischaracteristic including the articulation of science,enhanced understanding of positive health versus illness,emphasised personalisation of all medical services aswell as strong patient empowerment and essential respon-sibility of every person, at individual and communitylevels. “All for one and one for all”—a smart but perhaps abit naive slogan introduced by the Three Musketeers fitswell to the philosophy of the person-centred medicine.Therefore, a realisation of those ideas demands cleardefinitions and validated strategies to reach a reasonablelevel of maturity in health care [7].

Individualised medicineA great strength of individualised medicine (IM) is toprovide a holistic and integrative approach for medicalcare. IM comprises curative, rehabilitative and prevent-ive examination as well as treatment methods custo-mised for the individual and the patient [8]. IM wellrecognises a multidimensional interaction of internaland external risk factors, genetic background, age,gender, environmental risk factors, lifestyle, culture andbeliefs as well as social status in the overall predispos-ition of individuals to specific diseases, the diseasedevelopment, the natural course of disease and theresponse to therapeutic intervention. These factors varyfrom individual to individual. Contextually, IM aims tocategorise patients into clinically relevant subgroups

(that is the content of the “Stratified medicine” —seebelow). Hence, at the heart of the concept of IM is astratification that “individualises” a one-size-fits-allstandardised intervention into a group-specific inter-vention. Less clear concepts and approaches areprovided by IM towards “predictive and preventivemedicine”—see below.

Stratified medicineStratified medicine means looking at large groups ofaffected individuals (e.g. cancer patients) to try and findways of predicting which treatments/patient sub-typesare likely to respond to. Specifically in cancer, it involveslooking in detail at the cancer cells and their geneticmake-up. The purpose of the approach is to find outwhich treatment algorithms are more likely to work [9].Patient stratification is one step towards individualisedpatient treatments and so-called “personalised medicine”—see below.

Personalised medicineThe term “personalised medicine” is the keyword torefer to the best possible, most optimal and innovativemedical approaches in the early twenty-first century, tojustify grant applications and to receive dedicated bud-gets. However, in order to make anticipation by persona-lised medicine as realistic as possible, this term shouldbe pragmatically sub-divided into its clear subcategories,namely “semi-personalised” versus “true personalised” asit has been discussed and published elsewhere in scien-tific literature [10].“Semi-personalised medicine” compromises between

standardisation and individualisation in medicine, thefirst step of which is the stratification of big patient-groups according to certain well-known characteristics(e.g. specific biological characteristics of the tumour). Inthe next step, individual patients within the group aretreated according to the algorithms adapted to the entirestratified group. Consequently, the treatment efficacyvaries from patient to patient within the group, since alimited number of characteristics in common is consid-ered by the treatment algorithm; all other individualcharacteristics are not taken into account but maysufficiently impact individual outcomes.“True personalised medicine” is based on the “individ-

ual patient profile” (see “Predictive, preventive andpersonalised medicine (PPPM)” section) directing to atailored therapy that maximises the efficacy for that onepatient in particular.However, a disadvantage of “personalised medicine” is

that its contents are adapted to the needs of disease carefor treatments of diseased individuals and individualpatient cohorts but not for health care of individuals to

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maintain in a good mental and physical shape avoidingclinical manifestation of diseases.

Precision medicineThe terms precision, personalised and individualisedmedicines are often used interchangeably [11]. Precisionmedicine is a concept of therapeutic and preventivemodality for disease that takes into account individualvariability in genes, environment and lifestyle. It refersto the tailoring of medical treatment to the individualcharacteristics of each patient [12]. Precision medicine isconsidered a relatively new approach in disease andhealth care, although it has been around for a while andhas limited application in certain fields of medicine suchas blood transfusion and organ transplantation. Further,precision medicine faces a number of serious challengesthat need to be addressed [13–18] as summarised below.

a) Knowledge gap: Extensive and costly long-termeducation is required for all health care systemauthorities, physicians and participants to fullyunderstand the dynamic and potential objectivesof precision medicine.

b) Authority and interpretation: Even for the fieldspecialists, an interpretation of DNA data forindividual health outcomes remains sophisticatedand the problem of interpretability continues togrow. Consequently, many doctors are simply notable to make sense of genetic tests and tocommunicate the results accurately to their patients.

c) Data storage: Gene sequencing of an individualproduces massive amounts of data. The sequencingof thousands, if not millions, of people will produceunimaginable amount of data. How will we storethe data and effectively analyse to derive usefulinformation and to interpret the data?

d) Pathogenic mechanism: Many diseases have complexand multifactorial pathogenic mechanisms whichwould make it very difficult to identify a specificgene responsible for their manifestations.

e) Most technologies and equipment required foreffective implementation of precision medicine arestill in embryonic stages.

f ) Privacy/security: Cyberattack is increasingly a majorhurdle to maintaining privacy and security for allparticularly given the current state of world affairs.Such valid concerns are already well-recognised foreconomic, energy and defence sectors across theglobe. Precision medicine relies on massive publicand personal data requiring sophisticated andextensive infrastructure and technology. Thus,vulnerability due to breach of security and privacyviolation could have devastating consequences forthe successful implementation of precision medicine

[19] and data misusing, e.g. for economic andpolitical purposes with a consequent discriminationof affected individuals and even (sub)populationsinvolved in the database containing sensitive geneticinformation and family history amongst others.

g) Coordination and policies: For precision medicine tohave its greatest impact, federal and private healthinsurance companies have no option but to becomecomfortable with value-based drug pricing.

h) Variability of phenotypic features in population: It isdifficult, if not impossible, to detect, decipher andutilise phenotypic characteristics of every individualas indicators for diseases as seems to be proposedby precision medicine.

i) Data relevance: The usefulness of data gatheredfrom smaller groups may not be sufficient to makelarger population health recommendations.

j) Culture: Prevention of abuse of information forunintended purposes such as screening potentialpartners and denying insurance coverage is a seriousconcern. How will this affect the culture? Will we becultivating a different kind of racism, on a geneticbasis?

k) Ownership: Who will have ownership of the data?Will it be the government? It is noteworthy thatthe FDA has blocked companies from allowingindividuals to have access to their own geneticinformation. Will this change as part of the newinitiative?

l) Compliance: There is no binding protocol toguarantee that all individuals would follow therecommendations made by precision medicine sothe diseases could be prevented, controlled or cured.

m)Drug/device industry: Genetic research anddevelopment of treatment options have been verypromising and productive in the private sector. Howwill government involvement affect research? Willgovernmental agencies work cooperatively withthem or competitively?

n) Diversion from overarching goals of health caresystem: The focus and concentration of humanand financial resources on precision medicinemay divert attention and concerns of health caresystem from efforts to remedy the foundationalcauses of ill health such as poverty, obesity andeducation.

o) Health care costs: Genetic mapping of a population,and analyses of data, securing the information andderiving treatment recommendation are very costlywhich can be readily hampered by budgetaryconstraints of high dynamic economies. Further, thecosts of converting the intellectual capital totherapeutic modalities must also be taken intoaccount and built into the health care system.

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p) Finally, it is noteworthy that the concept ofprecision medicine may be a repackaging of theideals advanced by the human genome project in2000. The hope was to identify genetic markers forthe ultimate objective of developing novelbiomarkers and overcome perceived therapeuticdeficiencies and overcome the pressing issue ofnon-responders. However, this noble objective hasnot been fully materialised yet, leading one to thequestion: Is precision medicine “old vine in a newbottle”?

In conclusion, precision medicine could potentiallyimprove preventive methods and therapeutic options.However, a number of challenges remain as alluded toabove—see also the cartoon in Fig. 1. Precision medicinewill have to demonstrate consistency, coherence, com-prehensiveness, clarity and relevance to every individualand community impacted by these developments inmedical research and treatment. Will precision medicinedeliver all that it promises? With increasing shrinking offinancial resources, is it wise to invest millions of dollars/euros in an approach for which its risks versus benefits

ratio does not ring a satisfactory bell? Perhaps, stake-holders and authorities would be better off to furtherinvest and focus on the already established concepts of“predictive, preventive and personalised medicine.”

Predictive, preventive and personalised medicine(PPPM)The paradigm shift from “unPPPM” to “PPPM”The above described great plurality of approaches indi-cates a broad understanding of clear deficits which doexist in currently applied medical services and attemptsof diverse professional groups to remedy the deficits. Onthe other hand, there is an increasing level of under-standing that persisting deficits carry a fundamentalcharacter and, therefore, cannot be solved by superficialmodifications of health care systems facilitating individualtechnologies such as “cancer genomics” by “precisionmedicine.”Global deficits are well-defined and described else-

where as unpredictable, unpreventable and impersonalmedicine [20, 21]. It is evident that a paradigm shift isneeded to move from “reactive” to “predictive, prevent-ive and personalised medicine” as a new philosophy

Fig. 1 “Precision” itself does not guarantee for better understanding of an issue. An old wise dictum adopted by all European cultures/languageswarns—one cannot see the forest for the trees. Hence, technologically driven higher resolution of individual elements does not automatically meanthat you can better recognise the complex problem which you are looking for, particularly when the zoomed element (the tree) is prioritisedand/or pulled out from the overall context or zooming itself makes the complete picture (the forest/multifactorial issue) unreadable. Contextually,better understanding of the complexity in medicine is not guaranteed by “precision medicine” itself. Advanced health care demands a closecooperation between all issue-related fields, integration of multidisciplinary knowledge and innovative technologies based on long-term strategiesand concepts considering interests of patients, professionals and society at large

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covering both “health care” and “disease care”, promot-ing an integrated approach combining advantages of in-dividual bio/medical fields and technologies andconsolidating a multi-professional collaboration.New paradigm has been created by the EPMA experts

as published earlier [22]—see Fig. 2.

Particular emphasis on ethics in PPPMSometimes, we, living in the XXI century, forget whatwas taught when the first universities were established atthe birth of XI century: “Never discuss about names,”“Never enter an onomatomachia”, that is, never enter afight (in ancient Greek, μάχη, máchi) about names (inancient Greek, όνoμα, ónoma). Sometimes, the meaningsof the names “person-centred medicine,” “individualisedmedicine,” “stratified medicine,” “precision medicine,”“personalised medicine,” etc. are not so sharp; some-times, they intersect, but it is not clear until whichpoint.This is not a void and abstract “philosophical” ques-

tion (actually, over the centuries and the millennia, thephilosophers never thought that a question of nameswas a genuine philosophical question). This is a matterof money, a matter of grants, and a matter of power.This means that the onomatomachia now occurring inthe field of contemporary biomedicine is actually a warfor money and for power. But the citizens, in particulara subset of them, that is, the diseased citizens, are totallydisinterested about it, even if, unfortunately, negativeside effects of this war affect them. Citizens areinterested in a personalised care, whatever this couldprecisely mean [23].

This means that beside a scientifically well-foundedmedical approach facing their unique potential or actualdisease, they wish that their unique biography could betaken into account as well. Yet let us put aside for awhile the biographical part (i.e. the age, gender, cultural,ethnic, religious, socio-economic diversity) of an actualor potential patient, even if we know, from epigenomics,that patients’ lifestyles and the environments in whichthey live are extremely impacting their quality of life andtheir actual or potential diseases. Let us focus on the“medical” part.A citizen with an actual or potential disease wants a

medicine in which he/she is at the centre, a medicinewhich is tailored on his/her polymorphism, a medicinewhich is able to provide him/her with the right therapy,in the right dose, at the right moment, for the rightperiod of time. But he/she also wants a medicine whichis able to predict and prevent possible diseases. He/sheis not interested in the way in which this kind of medi-cine is called. But he/she is interested in understandingwhy it is called in that way, in order to appreciate itspotential ability to restore health. And this is the realadvantage of speaking in terms of predictive, preventiveand personalised medicine: the actual or potential pa-tient understands what is going on!Nevertheless, there is something more. The PPPM

lends itself to an over-arching umbrella under which themain ethical issues of contemporary biomedicine couldbe positively tackled. Certainly, a predictive and prevent-ive approach could imply several ethical problemslinked, for example, to overdiagnosis and overtreatment,detection of incidental findings, psychological burden

Fig. 2 Paradigm shift from “reactive” to “predictive, preventive and personalised medicine”

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and severe existential choices connected with the know-ledge of the probability of a possible disease affecting usor our offspring and lineages, or connected with ourreproductive choices, etc. Contextually, PPPM plays acrucial role as the optimal medical partner of a seriousethical counselling (and here, the patient’s biographyplays its main role) offered to actual or potential indi-vidual patients, in order to empower them to make aninfirmed choice about the diagnostic, surveillance ortherapeutic path to take, especially whenever these pathsintersect ethical or existential problematic situations thatthey have to solve [24].

Towards scientific excellence and practical PPPMimplementation: special professional focuses by the EPMAThis subsection is based on the well-elaborated PPPMaspects evidently advancing medical sciences and healthcare. Corresponding professional statements have beenapproved by the association within the fundamentaldocument resulting from the EPMA Summit 2014 underthe auspices of the presidency of Italy in the EU [6].

PPPM in cancer: the key questions puzzling medicalsciences and advancing health careThe majority of people may carry hardly detectablemicro- and asymptomatic tumour lesions as it has beendemonstrated by a series of detailed autopsy studies.However, those lesions do not necessarily progress intoclinically manifest oncologic diseases. Furthermore, thereis a phenomenon of the so-called metastatic inefficiency,due to less than 1 % of all disseminated and circulatedtumour cells which have a potential to form secondaryand distanced tumours (metastatic disease) [25]. Con-textually, the key question puzzling modern predictive,preventive and personalised medicine in oncology is howto predict and effectively protect against clinical manifest-ation of the disease by distinguishing between “silent” car-riers of tumour lesions and patients who are predisposedto a disease development and progression. The clue mightbe a “fertile” microenvironment that effectively supportsthe tumorigenesis, tumour invasiveness and aggressivemetastatic disease [26]. The mechanisms “fertilising” themicroenvironment for the cancer advancement arewell-addressed by innovative PPPM strategies in can-cer [26–29].

PPPM advancements in CVD management: a global healthissueCurrently, the CVD-related health burden is the mostsevere in developed countries and becomes overgrownin developing countries as well. The main reason for thatis that the chronic disease stages, multifactorial diseasesand comorbidities are not adequately addressed, sincethey do not follow the PPPM principles in currently

practised health care systems [30]. An advanced CVDmanagement is needed at both population and individuallevels considering complex cardiovascular risk factors,co-morbidities, individualised patient profiles, optimisedscreening programmes and innovative preventive strat-egies. Chronic suboptimal health conditions such as pri-mary vascular dysregulation (Flammer syndrome) maybe relevant for a number of predispositions and severepathologies with poor outcomes [31–33]. Consequently,the promotion of PPPM in CVD management is a globalhealth issue [34–36].

Global epidemic of diabetes type 2—twenty-first centurydisaster and PPPM solutionsCurrent epidemiologic studies report about over 400million of diabetes mellitus (DM) diseased patientsworldwide. A big portion of DM cases remains undiag-nosed. More and more teenagers are affected by DMtype 2. The global epidemic of DM type 2 places analarming burden on health care systems. The conse-quent challenges and costs overload both developed anddeveloping countries and economies. An effective imple-mentation of PPPM concepts to diabetes care is duelong ago. EPMA emphasises the need to address theall-encompassing complex approach for populationscreening, primary, secondary and tertiary care bene-fiting non-diseased individuals, predisposed subgroupsand affected patient cohorts including those withcomorbid pathologies such as CVD, cancer, andneurological, neuropsychiatric and neurodegenerativediseases (NNND) amongst others [6, 35, 37, 38].

PPPM advancing the comprehensive area of NNNDIn a very few years, NNND are predicted to representthe majority of socially and economically devastatingdisorders and diseases. Multifactorial physical and cogni-tive disability of NNND-affected patient cohorts resultsfrom individual interplay of genetic, epigenetic andenvironmental risk factors. Contextually, the compre-hensive area of NNND demands new strategies whichwould create a robust platform for the cost-effectivemedicine of future NNND management [39–42]. Conse-quently, the advanced PPPM concepts do place particu-lar emphasis on primary prevention by the identificationof predisposed individuals, improved patient stratifica-tion and treatments tailored to the person [6]. However,new regulations and innovative reimbursement pro-grammes are mandatory to prompt an effective imple-mentation of the above listed concepts.

Rare disease (RD) management: proof-of-principles forpersonalised medical careAlthough an entire spectrum of RDs affects many mil-lions of people worldwide (e.g. in Europe, there are at

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least 30 million patients), currently, no appropriate diag-nostic and treatment approaches are available for mostof afflicted with individual RDs. The majority of RDs canbe diagnosed in prenatal and early postnatal periods.Due to the genetic background of most RD pathologies,the multimodal diagnostic and treatment approachespropagated by PPPM are instrumental for personalisa-tion of RD management [43].

Ancient medical traditions “reinforced” by innovative PPPMconceptsPPPM creates a unique platform for “reinforcing” trad-itional approaches of the ancient medicines (TCAM).PPPM-TCAM hybrid demonstrates a great potential inperson-centred and participatory medicine, disease pre-diction in individuals with suboptimal health condition,targeted prevention and individualised treatments. Ifproperly designed, PPPM-TCAM approach may be ofparticular value for health care systems that empowerscommunities and individuals [3, 44].

Application of PPPM to the pain management benefiting allmedical fieldsPain management is the central issue for a variety ofsyndromes, acute, chronic and systemic disorders. Paindiagnostics and treatment are highly individual involvedin a wide spectrum of suboptimal health conditions,early and advanced stages of developing pathologies andcollateral diseases such as CVD, NNND, diabetes, andcancer. Application of PPPM concepts to advancedpain management demands multidisciplinary expertiseconsidered in the context of improved health careeconomy and policy and direct benefits to the patient[45–47].

Impacts of the oral and dental health: novelty by PPPMconceptsOn the one hand, dental diseases are frequently causedby systemic disorders such as diabetes mellitus. On theother hand, dental and oral pathologies are both earlyindicators and risk factors for a variety of multifactorialdiseases. This includes pre-term birth, a spectrum ofvascular pathologies, stroke, heart and lung disease, dia-betes mellitus with comorbidities, some types of cancer,neurological disorders and several mental disorders suchas depression, anxiety, anorexia and even bulimia.Therefore, investigation of the cause-and-effect relation-ships between oral and dental diseases on the one handand multifactorial systemic disorders on the other handis a prerequisite for predictive, preventive and persona-lised medicine in the multidisciplinary fields of dentaland oral health care [48–52].

Environmental factors in a sensitive balance between healthand diseaseThere is a highly sensitive interplay between a geneticcomponent, epigenetic regulations and environmentalfactors that determines a sensitive balance betweenhealth and disease in individuals. Unfortunately, envir-onment is still a largely neglected topic in health care.PPPM approach aims to develop an appropriate know-ledge and technological skills for promoting affordablestrategies in the emerging fields of environmental riskfactors, epidemiology, healthy lifestyle, individualisednutrition, food technology and culture in a framework ofcost-effective health care [29, 47, 53–55].

Robust PPPM platform to advance regenerative medicinePrediction and personalisation in regenerative medicineare prerequisites for improved individual outcomes. Hence,in order to optimally match the donor to recipient andassess individual risks, a successful transplantation requiresvalid pathology-specific pre- and post-transplantation bio-marker panels tailored to the individual. Long waiting listsof patients worldwide reflect major problems and currentdeficits, which require PPPM-related solutions advancingthis medical area on the global scale [6]. Individual compo-nents of the overall management leading to substantiallyincreased allograft survival and decreased patient morbid-ity are an improved donor-recipient matching, individualrisk assessment for chronic allograft damage, predic-tion of graft accommodation and creation of personalisedimmunosuppressive algorithms.

Body culture and sports medicine (BCSP) effectivelypromoted by PPPMPPPM strategies in BCSP are based on optimisation ofthe relationship between individual genetic predispositionsand modifiable risk factors (nutrients, physical activity,lifestyle, etc.). Therefore, the main tools are individualisedphysical exercises and therapy algorithms, healthy balancebetween body tension and relaxation, optimised sleepalgorithms according to individual circadian rhythm, in-novative rehabilitation approaches, amongst others. Anti-doping control and effective measures are mandatory forPPPM implementation in advanced BCSP. High-qualityresearch based on measurable effects utilising multilevelbiomarker panels is effectively promoted by PPPM inBCSP with a particular focus on individually tailored inter-ventions [56–59].

Translational medicine: a powerful bridge between PPPMscience and implementationThere are many scientific fields which, on a daily basis,provide a great knowledge potentially useful for advancedmedical services. However, a number of scientific articlesand valuable patents remain unused. The “bottleneck”

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between the sciences and application has many reasonsincluding economic circumstances and missing politicalregulations. In order to effectively promote the transla-tional medicine as the “catalyser” for practical implemen-tation of the accumulated scientific achievements, EPMAcreates a robust platform for an effective dialogue betweenPPPM relevant professional groups on the one side, andindustry and policy-makers on the other side—for moreinformation, see the main documents of the association[6, 35]. The main goal is to translate knowledge fromstudies at the bench side to care at the bedside by follow-ing mechanism: from discovery to health application, toevidence-based guidelines, to advanced health care ser-vices and finally to health impacts for the patient [60, 61].

Information and communication technologies (ICT)resulting in cost-effective modernisation of health careA holistic presentation of individuals and discoursedhealth condition by ICT approach implies a redesign ofhealth care services. The ICT support is the prerequisitefor an effective PPPM by disease modelling, individua-lised patient profiles, optimised diagnostic and treatmentapproaches. The ICT tools include mathematical model-ling methods, such as probabilistic relational models andprocess models, prediction of a disease development,precise patient stratification, creation of the multimodaldiagnostic approaches, elaboration of the best possibletherapy algorithms, an estimation of individual outcomes,distanced patient monitoring, advanced avatar technolo-gies, and bid data management amongst others. Con-textually, ICT is anticipated to result in profound andcost-effective modernisation of health care benefitingthe patient, health care providers and society at large[28, 29, 62–66].

The crucial role of multilevel diagnostics in PPPMAccumulating evidence demonstrates that an ideal bio-marker does not exist. The role of multilevel diagnosticsis to provide maximum clinically relevant informationby utilising pathology- and stage-specific biomarkerpanels at the level of medical imaging, subcellular im-aging, multi-omics and relevant hybrid technologies.Integrating this information allows for targeted preventionand personalised treatment regimes, avoiding unnecessarydrug toxicity, decreasing negative side-effects and redu-cing morbidity [27–29, 62, 67–69].

Laboratory medicine in PPPM concepts: from passiveassistance to active advisingDelayed intervention, untargeted medication, overdosedpatients and ineffective treatments, amongst others, arethe deficits in currently pursued medical services thatdemand a revised role of laboratory medicine in healthcare systems. The laboratory services should become

more complex, advancing multifactorial analysis. Such acomplex analytics should result in recommendationsand active advising for clinicians in order to more accur-ately interpret health-related data of the individual/patient.Therefore, an effective ICT support (see the “Informationand communication technologies (ICT) resulting incost-effective modernisation of health care” section)is mandatory. Practical implementation of novel andcomplex laboratory tests certainly should be consideredfrom the viewpoint of their reasonability, cost-effectivenessand value added to a data interpretation. Smart laboratoryinvestigation strategies and all-encompassing data interpret-ation are essential for an appropriate relationship betweenlaboratory medicine and clinicians acting hand-in-hand as the decision makers responsible for betterindividual outcomes [70–75].

Well-regulated biobanking and biopreservation is pivotalfor future progress in PPPMFor the future progress in development of novel bio-marker panels, predictive and prognostic technologiesand personalisation of treatment regimes, an internation-ally valid biobanking and biopreservation are essential. Aproper creation of that is currently an ongoing process inPPPM [66]. Considering individual types of biologicalmaterial (tissue, saliva, blood and cell samples, DNA,RNA, proteins, metabolites, etc.), the major challengesare due to:

– Consideration of ethical aspects includingprivacy- and security-related issues [76, 77]

– Adequate national and international regulations– Optimised protocols for collecting, storing and

retrieving the samples– High analytical quality of all the process of

biobanking and biopreservation– Adequately organised clinical/patient databases.

An effective support by the advanced ICT systems forsmoothly run processing and adequate data interpret-ation is crucial for the clinical utility of biobanks [66].

Design of professional interactome in PPPMPPPM carries highly multi- and interdisciplinary characterand demonstrates high level of international cooperation.Consequently, related networking demands an effectiveinteraction amongst professional groups as well as be-tween health care professionals and patient groups andpolicy-makers. All these groups currently do “speak differ-ent languages,” which may create some communicationbarriers, however, reinforcing each group’s perspective toreach higher level of understanding and cooperation inPPPM framework. The specific output of this designactivity is the so-called professional interactome [78]. The

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PPPM-related interactome represents the most optimalmodel of health care organisation with significantly in-creased quality of multilevel communication and cooper-ation resulting in improved individual patient outcomesand health care economy (see the “Advanced businessmodels for PPPM concepts in health care” section).

Education as the heart of the PPPM-related scientificexcellence and successful practical implementationThe ultimate goal is to create a new culture in the healthcare sector and to promote high level of professionalismby new generations of healthcare-givers who will be cap-able to implement an all-encompassing approach to

Table 1 Conclusions and expert recommendations

Term Advantages Limitations Optimal application and unique niche

Traditional,complementaryand alternativemedicine, TCAM

Increases the own repair capacityof the human body; deals withnatural products and physiologicalapproaches; is dedicated to diseaseprevention and well-being; highlyeffective at the level of suboptimalhealth condition

Less effective for disease care; inmanifest pathologies can be appliedto complement conventionaltreatments such as surgery,chemo-therapy, etc.; cultural barrierscan exist when TCAM is introducedby the country of origin to othercountries with sufficiently differentcultural habits

➢ Diagnosis and treatment ofsuboptimal health conditions

➢ Cost-effective preventive medicine➢ Emphasises well-being➢ Pain management➢ Complementary treatments➢ Cultural traditions of the country

of origin

Person-centredmedicine, PCM

Promotion of health as a state ofphysical, mental, social and spiritualwell-being; potential for diseasereduction; emphasis on scienceand humanism; PCM promotesapproaches to health improvement,respect and responsibility atindividual and community levels

Realisation of the ideals promotedby PCM demands clear definitionsand validated strategies

➢ Health care philosophy➢ Mental maturation of society at large➢ Integration of sciences and humanism➢ Promotion of health➢ Promotion of respect and responsibility

in the society

Individualisedmedicine, IM

IM propagates a holistic approachby acknowledging multidimensionalinteraction between internal andexternal risk factors which vary fromindividual to individual.

IM is clearly focused onindividualisation of standardisedintervention, but it provides lessdeveloped concepts of predictiveand preventive medicine, if any.

➢ Holistic approach to standardisedintervention

➢ Patient categorisation and modelling

Stratifiedmedicine, SM

More targeted treatments accordingto individual patient subtype;stratified treatment algorithms

Although being an extremelyimportant instrument, SM representsjust one step towards “personalisedmedicine.”

➢ Cohort subgrouping➢ Patient stratification

Personalisedmedicine, PM

Actually considered best possiblemedical treatments adapted to theneeds of the patient

Concepts of PM are adapted to“disease care” but not to “healthcare.”

Semi-personalised medicinecompromising between standardisationand individualisation in medicine

Precision medicine,PrecMed

PrecMed attracts attention ofpolicy-makers to problems persistingin medical services; additionallyreleased budgets in medicalsciences; increased publicity fordisease care; potentially increasedcooperation level between individualmedical fields

Politically motivated initiativeutilising advantages of alreadyexisting and above listedapproaches; strong limitations byselectively promoted technologicalfocuses (e.g. genomics); unclearintegration strategies in medicine;unclear cost-effectiveness, benefits toindividual patient cohorts and overallhealth care economy

➢ Potentially improved clinical impactsof specific areas such as genomics

➢ Potential technological integrationin medical fields

➢ Potentially improved outcomes insome patient cohorts

Predictive preventiveand personalisedmedicine, PPPM

PPPM is a really complexall-encompassing approachcombining advantages of theabove listed individual approachesand minimising their specificdisadvantages; clear conceptsdemonstrating the highest level ofmaturity; the most optimal strategiesconsidering interests of healthyindividuals, subpopulations, patientcohorts, health care systems andsociety as a whole.

PPPPM is considered as the“medicine of the future” whichneeds the paradigm change forentire spectrum of medical researchand services, improved professionaland general educational levels, neweconomic and application modelsfor both disease and health care.

➢ Desirable versus current health caresystems

➢ Predictive medicine➢ New spectrum of screening programmes➢ Targeted prevention➢ Currently unmet needs of healthy

subpopulations and patient cohorts➢ Cost-effective medical services and

optimised health care economy➢ New dimension of professional interests➢ New scale of the knowledge integration➢ Highly motivated technological innovation➢ Highly motivated interdisciplinary and

multidisciplinary cooperation➢ Individualised patient profiling➢ Active participation of patients in the

health care process

Golubnitschaja et al. The EPMA Journal (2016) 7:23 Page 9 of 13

patient care recognising the complexity and individualityof the human being. In order to promote innovativeeducational programmes, the following worldwide pion-eer initiatives have been developed:

– The EPMA Journal regularly updates informationabout medical innovations and advanced healthcare providing expert recommendations inpredictive diagnostics, targeted preventivemeasures and individualised treatment algorithms(https://epmajournal.biomedcentral.com/ andhttp://www.springer.com/biomed/journal/13167).

– Advances in predictive, preventive and personalisedmedicine (http://www.springer.com/series/10051):this book series, launched in 2012, provides anoverview of complex strategies, innovativetechnologies, novel biomarker panels, andmultidisciplinary aspects of advanced biomedicalapproaches in individual PPPM areas and healthcare as a whole. New technologies and guidelinesare provided for medical ethics, early and predictivediagnostics, targeted prevention, treatments tailoredto the person, health care organisation andeconomy. This book series is intended to serve as areference source for multidisciplinary research andthe health care industry with special emphasis onadvanced health promotion and cost-effectivetreatment of diseases.

Advanced business models for PPPM concepts in health careIf left unchanged, a long-term poor cost-effectivenessmay lead to economic collapse of current health caresystems with persisting archaic business models. AcrossEurope, there is a great diversity of systems, paymentmodels and reimbursement schemes in health care [72].This imposes a highly fragmented market. On the onehand, there is a need for policy dialogue in order toachieve improved structure and delivery. On the otherhand, advanced business models are required, in orderto motivate

– Healthcare-givers to apply more individualiseddiagnostic and treatment approaches

– Healthy individuals and patients to acceptgreater responsibility towards their own healthcondition

– Industry to create novel products for health support,promotion and monitoring

– Policy-makers for smart long-term regulations inhealth care sector such as an effective promotion ofincreased health literacy in population, advancedscreening programmes and new reimbursementmodels for individual subpopulations andprofessional groups

– Finally, the society at large to reinvest budgetsfocused on the most cost-effective health promotionand primary health care.

In view of economic strain and the ageing populations,PPPM-related innovation in health care systems is crit-ical for keeping the high quality of health care affordableand sustainable on European and global scale. Since itsvery beginning, EPMA is systematically working on theeconomy of PPPM that is pivotal for advancing healthcare on European and global scale [6, 8, 20–22, 28, 30,35, 37, 40, 71, 72, 79–82].

Conclusions and expert recommendationsConcluding remarks are summarised in Table 1 in formof advantages and limitations listed for individual typesof medicines analysed in this paper followed by recom-mendations for their most optimal application.

AbbreviationsCVD: Cardiovascular disease; DM: Diabetes mellitus; EPMA: EuropeanAssociation for Predictive, Preventive and Personalised Medicine;IM: Individualised medicine; NNND: Neurological, neuropsychiatric andneurodegenerative diseases; PCM: Person-centred medicine; PM: Personalisedmedicine; PPPM: Predictive, preventive and personalised medicine;PrecMed: Precision medicine; RD: Rare disease; SM: Stratified medicine;TCAM: Traditional, complementary and alternative medicine

AcknowledgementsThe position paper is created on behalf of the European Association forPredictive, Preventive and Personalised Medicine, EPMA, Brussels. Thenominated working groups (authors of the position paper) thank allEPMA members for their excellent professional expertise and a series ofPPPM-related articles to which current paper refers.

FundingNo funding has been provided.

Availability of data and materialsData sharing not applicable to this article as no datasets were generated oranalysed during the current study.

Authors’ contributionsAll authors have performed literature search and equally contributedto the concepts presented in the paper. OG has drafted the paper.BB, GB, WW, RB, MK, KK, MM and VC have contributed to the contentsof individual subsections. All authors read and approved the finalmanuscript.

Competing interestsThe authors declare that they have no competing interests.

Consent for publicationNot applicable.

Ethics approval and consent to participateNot applicable.

Author details1European Association for Predictive, Preventive and PersonalisedMedicine, Brussels, Belgium. 2Radiologic Department, RheinischeFriedrich-Wilhelms-University of Bonn, Sigmund-Freud-Str. 25, 53105Bonn, Germany. 3Breast Cancer Research Centre, RheinischeFriedrich-Wilhelms-University of Bonn, Bonn, Germany. 4AugustaUniversity, Augusta, GA, USA. 5Department of Surgery, School ofMedicine, Augusta University, Augusta, GA, USA. 6Dipartimento di

Golubnitschaja et al. The EPMA Journal (2016) 7:23 Page 10 of 13

Scienze Biomediche e Chirurgico Specialistiche, Università di Ferrara, ViaFossato di Mortara, 64A, 44121 Ferrara, Italy. 7Institute for AdvancedStudy, Technische Universität München, Garching bei München,Germany. 8School of Medical Sciences, Edith Cowan University, Perth,Australia. 9Beijing Municipal Key Laboratory of Clinical Epidemiology,Capital Medical University, Beijing, China. 10WHO Expert Panel (Member),Geneva, Switzerland. 11Global Health Epidemiology Reference Group(GHERG), Edinburgh, UK. 12Clinical hospital “Pheophania” of State AffairsDepartment, Kyiv, Ukraine. 13Zabolotny Institute of Microbiology andVirology, National Academy of Sciences of Ukraine, Kyiv, Ukraine.14European Medical Association, Brussels, Belgium.

Received: 24 September 2016 Accepted: 11 October 2016

References1. Xue CC. Traditional, complementary and alternative medicine: policy and

public health perspectives. Bull World Health Organ. 2008;86(1):77–8. doi:10.2471/BLT.07.046458.

2. Fokunang CN, Ndikum V, Tabi OY, Jiofack RB, Ngameni B, Guedje NM,Tembe-Fokunang EA, Tomkins P, Barkwan S, Kechia F, Asongalem E,Ngoupayou J, Torimiro NJ, Gonsu KH, Sielinou V, Ngadjui BT, Angwafor 3rd F,Nkongmeneck A, Abena OM, Ngogang J, Asonganyi T, Colizzi V, Lohoue J,Kamsu-Kom. Traditional medicine: past, present and future research anddevelopment prospects and integration in the National Health System ofCameroon. Afr J Tradit Complement Altern Med. 2011;8(3):284–95.

3. Wang W, Russell A, Yan Y, Global Health Epidemiology Reference Group(GHERG). Traditional Chinese medicine and new concepts of predictive,preventive and personalized medicine in diagnosis and treatment ofsuboptimal health. EPMA J. 2014;5(1):4. doi:10.1186/1878-5085-5-4.

4. Lang CL, Wang MH, Hung KY, Chiang CK, Lu KC. Altered molecularrepertoire of immune system by renal dysfunction in the elderly: isprediction and targeted prevention in the horizon? EPMA J. 2013;4(1):17.doi:10.1186/1878-5085-4-17.

5. Kupaev V, Borisov O, Marutina E, Yan YX, Wang W. Integration of suboptimalhealth status and endothelial dysfunction as a new aspect for riskevaluation of cardiovascular disease. EPMA J. 2016;7(1):19. doi:10.1186/s13167-016-0068-0.

6. Golubnitschaja O, Costigliola V, EPMA. EPMA summit 2014 under theauspices of the presidency of Italy in the EU: professional statements.EPMA J. 2015;6(1):4. doi:10.1186/s13167-015-0026-2.

7. Roberti di Sarsina P, Tassinari M. Person-centred healthcare and medicineparadigm: it’s time to clarify. EPMA J. 2015;6(1):11. doi:10.1186/s13167-015-0033-3.

8. Fischer T, Langanke M, Marschall P, Michl S, editors. Individualized medicine,advances in predictive, preventive and personalised medicine, vol. 7. SpringerDordrecht Heidelberg New York London; 2015. ISBN 978-3-319-11718-8.

9. Realising the potential of stratified medicine. The academy of medicalsciences 2013, https://www.acmedsci.ac.uk/viewFile/51e915f9f09fb.pdf(viewed on September 16th 2016)

10. Marino N, Woditschka S, Reed LT, Nakayama J, Mayer M, Wetzel M, SteegPS. Breast cancer metastasis issue for the personalization of its preventionand treatment. Am J Path. 2013;183(4):1084–95. doi:10.1016/j.ajpath.

11. Jameson JL, Longo DL. Precision medicine—personalized, problematic, andpromising. N Engl J Med. 2015;372(23):2229–34. doi:10.1056/NEJMsb1503104.

12. Collins FS, Varmus H. A new initiative on precision medicine. N Engl J Med.2015;372(9):793–5. doi:10.1056/NEJMp1500523.

13. Rubin R. Precision Medicine: The future or simply politics? JAMA. 313(11):1089-91. doi:10.1001/jama.2015.0957.

14. Patel K. Precision medicine: pros & cons. February 1st 2015. https://kirtipatel.com/2015/02/01/precision-medicine-blessing-or-curse/. Accessed 21 Sept 2016.

15. What are some of the challenges facing precision medicine and theprecision medicine initiative? https://ghr.nlm.nih.gov/primer/precisionmedicine/challenges. Accessed 21 Sept 2016.

16. Cardon LR, Harris T. Precision medicine, genomics abd drug discovery. HumMol Genet. 2016. doi:10.1093/hmg/ddw246.

17. Aerts HJWL. The potential of radiomic-based phenotyping in precisionmedicine: a review. JAMA Oncol. 2016. doi:10.1001/jamaoncol.2016.2631.

18. Nazha A, Sekeres MA. Precision medicine in myelodysplastic syndromesand leukemias: lessons from sequential mutations. Annu Rev Med. 2016;doi:10.1146/annurev-med-062915-095637.

19. Precision medicine initiative and data security. May 25th 2016. https://www.whitehouse.gov/blog/2016/05/25/precision-medicine-initiative-and-data-security. Accessed 21 Sept 2016.

20. Andrews RJ, editor. Too big to succeed—profiteering in American medicine.USA: iUniverse; 2013. ISBN: 978-1-14759-7130-9.

21. Andrews RJ, Quintana LM. Unpredictable, unpreventable and impersonalmedicine: global disaster response in the 21st century. EPMA J. 2015;6(1):2.doi:10.1186/s13167-014-0024-9.

22. Golubnitschaja O, editor. Predictive diagnostics and personalized treatment:dream or reality. New York: Nova; 2009. ISBN 978-1-60692-737-3.

23. Cornetta K, Brown CB. Perspective: balancing personalized medicineand personalized care. Acad Med. 2013;88(3):309–13. doi:10.1097/ACM.0b013e3182806345.

24. Boniolo G, Sanchini V, editors. Ethical counselling and medical decision-makingin the era of personalised medicine. A practice-oriented guide. SpringerDordrecht Heidelberg New York London; 2016. ISBN 978-3-319-27690-8.

25. Redig AJ, McAllister SS. Breast cancer as a systemic disease: a view ofmetastasis. J Intern Med. 2013;274(2):113–26. doi:10.1111/joim.12084.

26. Cox TR, Rumney RMH, Schoof EM, Perryman L, Høye AM, Agrawal A, Bird D,Latif NA, Forrest H, Evans HR, Huggins ID, Lang G, Linding R, Gartland A,Erler JT. The hypoxic cancer secretome induces pre-metastatic bonelesions through lysyl oxidase. Nature. 2015;522(7554):106–10.doi:10.1038/nature14492.

27. Golubnitschaja O and Sridhar KC. Liver metastatic disease: new conceptsand biomarker panels to improve individual outcomes. Clin Exp Metastasis.2016; doi:10.1007/s10585-016-9816-8.

28. Grech G, Zhan X, Yoo BC, Bubnov R, Hagan S, Danesi R, Vittadini G,Desiderio DM. EPMA position paper in cancer: current overview and futureperspectives. EPMA J. 2015;6(1):9. doi:10.1186/s13167-015-0030-6.

29. Golubnitschaja O, Debald M, Yeghiazaryan K, Kuhn W, Pešta M, Costigliola V,Grech G. Breast cancer epidemic in the early 21st century: evaluation of riskfactors, cumulative questionnaires and recommendations for preventivemeasures. Tumor Biol. 2016; doi:10.1007/s13277-016-5168-x.

30. Brunner-La Rocca HP, Fleischhacker L, Golubnitschaja O, Heemskerk F,Helms T, Hoedemakers T, Allianses SH, Jaarsma T, Kinkorova J, Ramaekers J,Ruff P, Schnur I, Vanoli E, Verdu J, Zippel-Schultz B. Challenges inpersonalised management of chronic diseases-heart failure asprominent example to advance the care process. EPMA J. 2016;7:2.doi:10.1186/s13167-016-0051-9.

31. Konieczka K, Ritch R, Traverso CE, Kim DM, Kook MS, Gallino A,Golubnitschaja O, Erb C, Reitsamer HA, Kida T, Kurysheva N, Yao K.Flammer syndrome. EPMA J. 2014;5(1):11. doi:10.1186/1878-5085-5-11.

32. Golubnitschaja O, Debald M, Kuhn W, Yeghiazaryan K, Bubnov RV, GoncharenkoVM, Lushchyk U, Grech G, Konieczka K. Flammer syndrome and potentialformation of pre-metastatic niches: a multi-centred study on phenotyping,patient stratification, prediction and potential prevention of aggressive breastcancer and metastatic disease. EPMA J. 2016;7 Suppl 1:A25.

33. Konieczka K, Koch S, Binggeli T, Schoetzau A, Kesselring J. Multiple sclerosisand primary vascular dysregulation (Flammer syndrome). EPMA J. 2016;7:13.doi:10.1186/s13167-016-0062-6.

34. Iso H. Promoting predictive, preventive and personalized medicinein treatment of cardiovascular diseases. EPMA J. 2011;2(1):1–4.doi:10.1007/s13167-011-0075-0.

35. Golubnitschaja O, Costigliola V, EPMA. General report & recommendationsin predictive, preventive and personalised medicine 2012: white paper ofthe European association for predictive, preventive and personalisedmedicine. EPMA J. 2012;3(1):14. doi:10.1186/1878-5085-3-14.

36. Helms TM, Duong G, Zippel-Schultz B, Tilz RR, Kuck K-H, Karle CA.Prediction and personalised treatment of atrial fibrillation-stroke prevention:consolidated position paper of CVD professionals. EPMA J. 2014;5(1):15.doi:10.1186/1878-5085-5-15.

37. Mozaffari MS, editor. New strategies to advance pre/diabetes care:integrative approach by PPPM, advances in predictive, preventive andpersonalised medicine, vol. 2. Springer Dordrecht Heidelberg New YorkLondon; 2013. ISBN 978-94-007-5970-1.

38. Golubnitschaja O. Time for new guidelines in advanced diabetes care:paradigm change from delayed interventional approach to predictive,preventive and personalized medicine. EPMA J. 2010;1(1):3–12.doi:10.1007/s13167-010-0014-5.

39. Golubnitschaja O, Yeghiazaryan K, Cebioglu M, Morelli M,Herrera-Marschitz M. Birth asphyxia as the major complication in

Golubnitschaja et al. The EPMA Journal (2016) 7:23 Page 11 of 13

newborns: moving towards improved individual outcomes byprediction, targeted prevention and tailored medical care. EPMA J.2011;2(2):197–210. doi:10.1007/s13167-011-0087-9.

40. Mandel S, editor. Neurodegenerative diseases: integrative PPPM approach asthe medicine of the future, advances in predictive, preventive andpersonalised medicine, vol. 3. Springer Dordrecht Heidelberg New YorkLondon; 2013. ISBN 978-94-007-5865-0.

41. Sinnecker T, Kuchling J, Dusek P, Dörr J, Niendorf T, Paul F, Wuerfel J.Ultrahigh field MRI in clinical neuroimmunology: a potential contribution toimproved diagnostics and personalised disease management. EPMA J.2015;6(1):16. doi:10.1186/s13167-015-0038-y.

42. Polivka J, Polivka Jr J, Krakorova K, Peterka M, Topolcan O. Currentstatus of biomarker research in neurology. EPMA J. 2016;7:14.doi:10.1186/s13167-016-0063-5.

43. Özgüç M, editor. Rare diseases—integrative PPPM approach as themedicine of the future, advances in predictive, preventive and personalisedmedicine, vol. 6. Springer Dordrecht Heidelberg New York London; 2015.ISBN 978-94-017-9213-4.

44. Roberti di Sarsina P, Alivia M, Guadagni P. Traditional, complementary andalternative medical systems and their contribution to personalisation,prediction and prevention in medicine-person-centred medicine. EPMA J.2012;3(1):15. doi:10.1186/1878-5085-3-15.

45. Bubnov RV. Evidence-based pain management: is the concept of integrativemedicine applicable? EPMA J. 2012;3(1):13. doi:10.1186/1878-5085-3-13.

46. Arai YC, Yasui H, Isai H, Kawai T, Nishihara M, Sato J, Ikemoto T, Inoue S,Ushida T. The review of innovative integration of Kampo medicine andWestern medicine as personalized medicine at the first multidisciplinarypain center in Japan. EPMA J. 2014;5(1):10. doi:10.1186/1878-5085-5-10.

47. Moiseyenko YV, Sukhorukov VI, Pyshnov GY, Mankovska IM, Rozova KV,Miroshnychenko OA, Kovalevska OE, Madjar SA, Bubnov RV, Gorbach AO,Danylenko KM, Moiseyenko OI. Antarctica challenges the new horizons inpredictive, preventive, personalized medicine: preliminary results and attractivehypotheses for multi-disciplinary prospective studies in the Ukrainian “AkademikVernadsky” station. EPMA J. 2016;7:11. doi:10.1186/s13167-016-0060-8. Erratum in:EPMA J. 2016;7:17.

48. Cafiero C, Matarasso S. Predictive, preventive, personalised and participatoryperiodontology: “the 5Ps age” has already started. EPMA J. 2013;4(1):16.doi:10.1186/1878-5085-4-16.

49. Golubnitschaja O, Costigliola V. Dental health: EPMA recommendations forinnovative strategies. EPMA J. 2014;5 Suppl 1:A119.

50. Kunin AA, Evdokimova AY, Moiseeva NS. Age-related differences of toothenamel morphochemistry in health and dental caries. EPMA J. 2015;6(1):3.doi:10.1186/s13167-014-0025-8.

51. Tachalov VV, Orekhova LY, Kudryavtseva TV, Isaeva ER, Loboda ES.Manifestations of personal characteristics in individual oral care. EPMA J.2016;7:8. doi:10.1186/s13167-016-0058-2.

52. Qin X, Liu JY, Abdelsayed R, Shi X, Yu JC, Mozaffari MS, Baban B. The statusof glucocorticoid-induced leucine zipper protein in the salivary glands inSjögren’s syndrome: predictive and prognostic potentials. EPMA J. 2016;7:3.doi:10.1186/s13167-016-0052-8.

53. Trovato GM. Behavior, nutrition and lifestyle in a comprehensive health anddisease paradigm: skills and knowledge for a predictive, preventive andpersonalized medicine. EPMA J. 2012;3(1):8. doi:10.1007/s13167-012-0141-2.

54. Shapira N. Women’s higher health risks in the obesogenic environment: a gendernutrition approach to metabolic dimorphism with predictive, preventive, andpersonalised medicine. EPMA J. 2013;4(1):1. doi:10.1186/1878-5085-4-1.

55. Richter K, Acker J, Adam S, Niklewski G. Prevention of fatigue and insomniain shift workers—a review of non-pharmacological measures. EPMA J. 2016;7:16. doi:10.1186/s13167-016-0064-4.

56. Oja P, Titze S. Physical activity recommendations for public health:development and policy context. EPMA J. 2011;2:253–9.

57. Graf C. Preventing and treating obesity in pediatrics through physicalactivity. EPMA J. 2011;2(3):261–70. doi:10.1007/s13167-011-0091-0.

58. Schulte S, Rasmussen NN, McBeth JW, Richards PQ, Yochem E, Petron DJ,Strathmann FG. Utilization of the clinical laboratory for the implementationof concussion biomarkers in collegiate football and the necessity ofpersonalized and predictive athlete specific reference intervals. EPMA J.2016;7:1. doi:10.1186/s13167-016-0050-x.

59. Trovato FM, Catalano D, Musumeci G, Trovato GM. 4Ps medicineof the fatty liver: the research model of predictive, preventive,personalized and participatory medicine-recommendations for facing

obesity, fatty liver and fibrosis epidemics. EPMA J. 2014;5(1):21.doi:10.1186/1878-5085-5-21.

60. Younesi E, Hofmann-Apitius M. From integrative disease modeling topredictive, preventive, personalized and participatory (P4) medicine. EPMA J.2013;4:23. doi:10.1186/1878-5085-4-23.

61. Drucker E, Krapfenbauer K. Pitfalls and limitations in translation frombiomarker discovery to clinical utility in predictive and personalisedmedicine. EPMA J. 2013;4:7. doi:10.1186/1878-5085-4-7.

62. Hu R, Wang X, Zhan X. Multi-parameter systematic strategies for predictive,preventive and personalised medicine in cancer. EPMA J. 2013;4(1):2.doi:10.1186/1878-5085-4-2.

63. Lemke HU, Golubnitschaja O. Towards personal health care withmodel-guided medicine: long-term PPPM-related strategies andrealisation opportunities within “Horizon 2020”. EPMA J. 2014;5(1):8.doi:10.1186/1878-5085-5-8.

64. Berliner L, Lemke HU, VanSonnenberg E, Ashamalla H, Mattes MD, Dosik D,Hazin H, Shah S, Mohanty S, Verma S, Esposito G, Bargellini I, Battaglia V,Caramella D, Bartolozzi C, Morrison P. Model-guided therapy forhepatocellular carcinoma: a role for information technology inpredictive, preventive and personalized medicine. EPMA J. 2014;5(1):16.doi:10.1186/1878-5085-5-16.

65. Berliner L, Lemke HU, editors. An information technology framework forpredictive, preventive and personalised medicine, a use-case withhepatocellular carcinoma, advances in predictive, preventive andpersonalised medicine, vol. 8. Springer Dordrecht Heidelberg New YorkLondon; 2015. ISBN 978-3-319-12165-9.

66. Kinkorova J. Biobanks in the era of personalized medicine:objectives, challenges, and innovation: overview. EPMA J. 2016;7:4.doi:10.1186/s13167-016-0053-7.

67. Grech G, Grossman I, editors. Preventive and predictive genetics: towardspersonalised medicine, advances in predictive, preventive and personalisedmedicine, vol. 9. Springer Dordrecht Heidelberg New York London; 2015.ISBN 978-3-319-15343-8.

68. Hagan S, Martin E, Enríquez-de-Salamanca A. Tear fluid biomarkers in ocularand systemic disease: potential use for predictive, preventive andpersonalised medicine. EPMA J. 2016;7:15. doi:10.1186/s13167-016-0065-3.

69. Girotra S, Yeghiazaryan K, Golubnitschaja O. Potential biomarker panels inoverall breast cancer management: advancements by multilevel diagnostics.Pers Med. 2016;13(5):469–84. doi:10.2217/pme-2016-0020.

70. Waerner T, Thurnher D, Krapfenbauer K. The role of laboratory medicine inhealthcare: quality requirements of immunoassays, standardisation anddata management in prospective medicine. EPMA J. 2010;1(4):619–26.doi:10.1007/s13167-010-0053-y.

71. Golubnitschaja O, Watson ID, Topic E, Sandberg S, Ferrari M, Costigliola V.Position paper of the EPMA and EFLM: a global vision of the consolidatedpromotion of an integrative medical approach to advance health care.EPMA J. 2013;4(1):12. doi:10.1186/1878-5085-4-12.

72. Costigliola V. Healthcare overview: new perspectives, advances in predictive,preventive and personalised medicine, vol. 1. Springer DordrechtHeidelberg New York London; 2012. ISBN 978-94-007-4602-2.

73. Gahan PB. Circulating nucleic acids in early diagnosis, prognosis andtreatment monitoring, advances in predictive, preventive and personalisedmedicine, vol. 5. Springer Dordrecht Heidelberg New York London; 2015.ISBN 978-94-017-9167-0.

74. Abraham J-A, Yeghiazaryan K, Golubnitschaja O. Selective internalradiation therapy in treatment of hepatocellular carcinoma: newconcepts of personalization. Pers Med. 2016;13(4):347–60.doi:10.2217/pme-2016-0014.

75. Abraham J-A, Golubnitschaja O. Time for paradigm change in managementof hepatocellular carcinoma: is a personalized approach on the horizon?Pers Med. 2016;13(5):455–67. doi:10.2217/pme-2016-0013.

76. Boniolo G, Di Fiore PP, Pece S. Trusted consent and research biobanks.Towards a “new alliance” between researchers and donors. Bioethics.2012;26(2):93–100. doi:10.1111/j.1467-8519.2010.01823.x.

77. Sanchini V, Bonizzi G, Disalvatore D, Monturano M, Pece S,Viale G, Di Fiore PP, Boniolo G. A trust-based pact in researchbiobanks. From theory to practice. Bioethics. 2016;30(4):260–71.doi:10.1111/bioe.12184.

78. Golubnitschaja O, Lemke HU, Kapalla M, Kent A. Design in predictive,preventive and personalised medicine. In: Kuksa I, Fisher T, editors. Design forPersonalisation. London: Gower Publishing; 2017. in press.

Golubnitschaja et al. The EPMA Journal (2016) 7:23 Page 12 of 13

79. Ausweger C, Burgschwaiger E, Kugler A, Schmidbauer R, Steinek I, Todorov Y,Thurnher D, Krapfenbauer K. Economic concerns about global healthcare inlung, head and neck cancer: meeting the economic challenge of predictive,preventive and personalized medicine. EPMA J. 2010;1(4):627–31.doi:10.1007/s13167-010-0054-x.

80. Brown PM. Personalized medicine and comparative effectivenessresearch in an era of fixed budgets. EPMA J. 2010;1(4):633–40.doi:10.1007/s13167-010-0058-6.

81. Golubnitschaja O, Kinkorova J, Costigliola V. Predictive, preventive andpersonalised medicine as the hardcore of ‘Horizon 2020’: EPMA positionpaper. EPMA J. 2014;5(1):6. doi:10.1186/1878-5085-5-6.

82. Akhmetov I, Bubnov RV. Assessing value of innovative molecular diagnostictests in the concept of predictive, preventive, and personalized medicine.EPMA J. 2015;6:19. doi:10.1186/s13167-015-0041-3.

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